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1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020
BACKGROUND: The rapid spread of antimicrobial resistance among clinically isolated Enterobacterales (Eba) continues to threaten public health. Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam (AVI) inhibits class A, class C, and some class D serine β-...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752487/ http://dx.doi.org/10.1093/ofid/ofac492.1347 |
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author | Estabrook, Mark Arhin, Francis Sahm, Daniel F |
author_facet | Estabrook, Mark Arhin, Francis Sahm, Daniel F |
author_sort | Estabrook, Mark |
collection | PubMed |
description | BACKGROUND: The rapid spread of antimicrobial resistance among clinically isolated Enterobacterales (Eba) continues to threaten public health. Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases. ATM-AVI is being developed for use against drug-resistant isolates of Eba, especially those co-producing MBLs and other β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2017-2020 from pediatric and adult patients as part of the ATLAS global surveillance program. METHODS: Non-duplicate clinical Eba isolates were collected from 239 sites in 55 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2022 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. RESULTS: MIC(90) values for ATM-AVI of 0.12 µg/ml were observed for Eba isolates collected from both pediatric and adult patients. Against all Eba isolates, ≤8 µg/ml of ATM-AVI was sufficient to inhibit 99.97% (pediatric) and 99.95% (adult), whereas ATM alone inhibited only 72.0% and 75.9% of these isolates at ≤8 µg/ml, respectively (table). Among isolates that screened positive for an MBL, MIC(90) values were 0.25 µg/ml (pediatric) and 0.5 µg/ml (adult). Among MBL-positive isolates, ATM-AVI inhibited 100% (pediatric) and 99.9% (adult) at concentrations ≤8 µg/ml. In contrast, ATM alone only inhibited 19.0% (pediatric) and 25.3% (adult) of isolates carrying MBLs at ≤8 µg/ml. [Figure: see text] CONCLUSION: Based on MIC(90) values, ATM-AVI demonstrated potent in vitro activity against Eba isolated both from pediatric and adult patients. The capability of AVI to potentiate ATM against MBL-positive isolates warrants its continued development. DISCLOSURES: All Authors: No reported disclosures. |
format | Online Article Text |
id | pubmed-9752487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97524872022-12-16 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 Estabrook, Mark Arhin, Francis Sahm, Daniel F Open Forum Infect Dis Abstracts BACKGROUND: The rapid spread of antimicrobial resistance among clinically isolated Enterobacterales (Eba) continues to threaten public health. Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases. ATM-AVI is being developed for use against drug-resistant isolates of Eba, especially those co-producing MBLs and other β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2017-2020 from pediatric and adult patients as part of the ATLAS global surveillance program. METHODS: Non-duplicate clinical Eba isolates were collected from 239 sites in 55 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2022 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. RESULTS: MIC(90) values for ATM-AVI of 0.12 µg/ml were observed for Eba isolates collected from both pediatric and adult patients. Against all Eba isolates, ≤8 µg/ml of ATM-AVI was sufficient to inhibit 99.97% (pediatric) and 99.95% (adult), whereas ATM alone inhibited only 72.0% and 75.9% of these isolates at ≤8 µg/ml, respectively (table). Among isolates that screened positive for an MBL, MIC(90) values were 0.25 µg/ml (pediatric) and 0.5 µg/ml (adult). Among MBL-positive isolates, ATM-AVI inhibited 100% (pediatric) and 99.9% (adult) at concentrations ≤8 µg/ml. In contrast, ATM alone only inhibited 19.0% (pediatric) and 25.3% (adult) of isolates carrying MBLs at ≤8 µg/ml. [Figure: see text] CONCLUSION: Based on MIC(90) values, ATM-AVI demonstrated potent in vitro activity against Eba isolated both from pediatric and adult patients. The capability of AVI to potentiate ATM against MBL-positive isolates warrants its continued development. DISCLOSURES: All Authors: No reported disclosures. Oxford University Press 2022-12-15 /pmc/articles/PMC9752487/ http://dx.doi.org/10.1093/ofid/ofac492.1347 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstracts Estabrook, Mark Arhin, Francis Sahm, Daniel F 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title | 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title_full | 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title_fullStr | 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title_full_unstemmed | 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title_short | 1717. In Vitro Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2017-2020 |
title_sort | 1717. in vitro activity of aztreonam-avibactam against enterobacterales isolated from pediatric and adult patients collected during the atlas global surveillance program, 2017-2020 |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752487/ http://dx.doi.org/10.1093/ofid/ofac492.1347 |
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